US7309691B2 - Combined pharmaceutical preparation containing LHRH-analogous substances and anti estrogens for treating gynaecological disorders - Google Patents
Combined pharmaceutical preparation containing LHRH-analogous substances and anti estrogens for treating gynaecological disorders Download PDFInfo
- Publication number
- US7309691B2 US7309691B2 US09/117,357 US11735798A US7309691B2 US 7309691 B2 US7309691 B2 US 7309691B2 US 11735798 A US11735798 A US 11735798A US 7309691 B2 US7309691 B2 US 7309691B2
- Authority
- US
- United States
- Prior art keywords
- lhrh
- patient
- raloxifen
- analogue
- administration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related, expires
Links
- 230000001833 anti-estrogenic effect Effects 0.000 title description 2
- 239000000126 substance Substances 0.000 title description 2
- 229940046836 anti-estrogen Drugs 0.000 title 1
- 239000000328 estrogen antagonist Substances 0.000 title 1
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical class C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 claims abstract description 64
- 230000000694 effects Effects 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims description 23
- AUYLVPGDOVEOML-UHFFFAOYSA-N [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-(piperidin-1-ylmethoxy)phenyl]methanone Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 AUYLVPGDOVEOML-UHFFFAOYSA-N 0.000 claims description 21
- 230000037396 body weight Effects 0.000 claims description 16
- 230000037182 bone density Effects 0.000 claims description 12
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 claims description 11
- QRYFGTULTGLGHU-NBERXCRTSA-N iturelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CCCCNC(=O)C=1C=NC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)CCCNC(=O)C1=CC=CN=C1 QRYFGTULTGLGHU-NBERXCRTSA-N 0.000 claims description 11
- 108010083551 iturelix Proteins 0.000 claims description 11
- 108700008462 cetrorelix Proteins 0.000 claims description 10
- SBNPWPIBESPSIF-MHWMIDJBSA-N cetrorelix Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 SBNPWPIBESPSIF-MHWMIDJBSA-N 0.000 claims description 10
- 229960003230 cetrorelix Drugs 0.000 claims description 10
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 claims description 9
- 102100024028 Progonadoliberin-1 Human genes 0.000 claims description 9
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 claims description 9
- 108010000817 Leuprolide Proteins 0.000 claims description 8
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical group CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 claims description 8
- 229960004338 leuprorelin Drugs 0.000 claims description 8
- 108010069236 Goserelin Proteins 0.000 claims description 7
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims description 7
- 239000000556 agonist Substances 0.000 claims description 7
- 239000002474 gonadorelin antagonist Substances 0.000 claims description 7
- 229940033942 zoladex Drugs 0.000 claims description 7
- WDYSQADGBBEGRQ-APSDYLPASA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-[(2r,3r,4r,5r,6s) Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)O[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O WDYSQADGBBEGRQ-APSDYLPASA-N 0.000 claims description 6
- 108010037003 Buserelin Proteins 0.000 claims description 6
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 claims description 6
- 229960002719 buserelin Drugs 0.000 claims description 6
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 6
- 108010092834 ramorelix Proteins 0.000 claims description 6
- 229950000277 ramorelix Drugs 0.000 claims description 6
- 230000002263 peptidergic effect Effects 0.000 claims description 4
- 239000002434 gonadorelin derivative Substances 0.000 claims 7
- 230000001627 detrimental effect Effects 0.000 claims 6
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 5
- 230000002401 inhibitory effect Effects 0.000 claims 3
- 238000011282 treatment Methods 0.000 abstract description 27
- 239000000262 estrogen Substances 0.000 abstract description 24
- 201000009273 Endometriosis Diseases 0.000 abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 11
- 201000004458 Myoma Diseases 0.000 abstract description 9
- 239000004480 active ingredient Substances 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 12
- 230000001076 estrogenic effect Effects 0.000 description 11
- 208000035475 disorder Diseases 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 210000004696 endometrium Anatomy 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 210000004291 uterus Anatomy 0.000 description 5
- 210000000988 bone and bone Anatomy 0.000 description 4
- 206010013935 Dysmenorrhoea Diseases 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 206010027514 Metrorrhagia Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010067572 Oestrogenic effect Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- VXYFNFAJVNPWCT-UHFFFAOYSA-N ethyl 2-(4-acetamidophenyl)-3-[[benzyl(methyl)amino]methyl]-7-[(2-methoxyphenyl)methyl]-4-oxothieno[2,3-b]pyridine-5-carboxylate Chemical compound C1=2SC(C=3C=CC(NC(C)=O)=CC=3)=C(CN(C)CC=3C=CC=CC=3)C=2C(=O)C(C(=O)OCC)=CN1CC1=CC=CC=C1OC VXYFNFAJVNPWCT-UHFFFAOYSA-N 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 208000000509 infertility Diseases 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 208000007106 menorrhagia Diseases 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229960004622 raloxifene Drugs 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 206010061692 Benign muscle neoplasm Diseases 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- -1 Droloxifen Chemical compound 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000033830 Hot Flashes Diseases 0.000 description 1
- 206010060800 Hot flush Diseases 0.000 description 1
- 206010030247 Oestrogen deficiency Diseases 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000011292 agonist therapy Methods 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 1
- 229960000766 danazol Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- XZEUAXYWNKYKPL-URLMMPGGSA-N ormeloxifene Chemical compound C1([C@@H]2[C@H](C3=CC=C(C=C3OC2(C)C)OC)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 XZEUAXYWNKYKPL-URLMMPGGSA-N 0.000 description 1
- 229960003327 ormeloxifene Drugs 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- a unit dose contains different amounts of active ingredient depending in each case on the form of administration.
- oral administration usually from 2 ⁇ g to 20 mg of LHRH analogue is administered per kg of body weight.
- the administration may be in solid or liquid form.
- the amounts of LHRH analogues are from 0.02 ⁇ g to 2.5 mg per kg of body weight.
- parenteral administration there is preferably used an isotonic sodium chloride or dextrose solution that optionally is adjusted with a buffer to a pH value of from 5 to 9, preferably to the pH value of the blood.
- Leuprorelin is preferably used orally at a dose of from 2 to 100 ⁇ g/kg of body weight (daily dose); one tablet contains preferably from 0.1 to 5.0 mg of Leuprorelin.
- the dose for parenteral administration is preferably from 0.02 to 1.0 ⁇ g/kg of body weight.
- Cetrorelix is used preferably in the form of a physiological saline with an amount of active ingredient of from 0.1 to 2.5 mg/kg of body weight.
- DE 43 42 092 also slow-release formulations of Cetrorelix are described.
- Buserelin is administered preferably in the following doses:
- the implant contains from 1 to 6 mg of Cetrorelix.
- Zoladex is preferably administered orally with a content of from 50 ⁇ g to 20 mg/kg of body weight and parenterally with a content of from 0.02 ⁇ g to 100 ⁇ g/kg of body weight or using a slow-release system (WO-A 93/24150).
- Anti-oestrogenic substances are used inter alia in tumour therapy.
- SERMs selective oestrogen-receptor modulators
- Any antioestrogen having tissue-selective oestrogenic activity may be used in accordance with the invention.
- Preferably used are those selected from the group Raloxifen, Droloxifen, Centchroman and derivatives thereof.
- Anti-oestrogens of the Raloxifen type are especially preferred.
- Raloxifen is 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo [b] thiophene.
- Raloxifen and its derivatives are used to increase bone mass.
- EP 0635 270 discloses that raloxifene is described in U.S. Pat. No. 4,418,068 and that EP-A-584952 discloses that raloxifene is useful in the inhibition or preventing of bone loss.
- the active ingredient content of the anti-oestrogen used in accordance with the invention is in the case of daily administration from 0.1 ⁇ g to 10 mg of antioestrogen per kg of body weight, depending on the form of administration.
- the anti-oestrogens may be administered intravenously, subcutaneously, intramuscularly, orally, intranasally or intravaginally. Slow-release formulations are also possible, in which case the amount released daily lies also within the above-mentioned range.
- the administration of the LHRH analogue and of the anti-oestrogen to the patient may be simultaneous and/or chronologically sequential.
- Various treatment regimes are possible:
- the LHRH analogue is first of all administered simultaneously with the tissue-selective anti-oestrogen over a particular period of time.
- the information given in 1 applies in respect of period and frequency of administration (daily or at greater intervals). Treatment is then continued with the anti-oestrogen only.
- the information given in 1 applies in respect of period and frequency of administration.
- the pharmaceutical combined preparation according to the invention is suitable especially for long-term treatment of endometrioses and myomas and other steroid(sex)-hormone-dependent disorders, since on the one hand the side effects that normally occur with an LHRH analogue (agonist or antagonist) treatment are avoided and on the other hand lost bone mass is rebuilt (for example in the case of administration of the tissue-selective anti-oestrogen after completion of an LHRH analogue treatment). At the same time the growth inhibition of the endometriosis is maintained without the endometrium in the uterus being stimulated.
- LHRH analogue agonist or antagonist
- Variant 1 has proved especially preferred for long-term therapy.
- the invention relates also to a packaging unit which, in the case of peptidergic LHRH analogues, comprises at least three components.
- the unit contains two spatially separately packaged active ingredients, one of which is an LHRH analogue or a combination of LHRH analogues, and the other of which is an anti-oestrogen having tissue-selective oestrogenic activity.
- the third component is an information leaflet for the simultaneous and/or chronologically sequential administration of the forms of administration.
- the invention relates also to the use of an LHRH analogue or a combination of LHRH analogues and an anti-oestrogen having tissue-selective oestrogenic activity for the treatment of gynaecological disorders, especially for the treatment of endometrioses and myomas.
- Fragments of endometrium were transplanted into different regions of the abdominal cavity of 60 animals.
- the result to be recorded was a complete regression of the endometriosis without a significant reduction in bone mass. At the same time there were no oestrogenic effects on the uterus.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/925,419 US20020032156A1 (en) | 1996-01-29 | 2001-08-10 | Pharmaceutical combined preparation and its use in the treatment of gynaecological disorders |
| US10/207,907 US20020198155A1 (en) | 1996-01-29 | 2002-07-31 | Pharmaceutical combined preparation and its use in the treatment of gynaecological disorders |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19604231A DE19604231A1 (de) | 1996-01-29 | 1996-01-29 | Pharmazeutisches Kombinationspräparat und seine Verwendung zur Behandlung von gynäkologischen Störungen |
| DE19604231.3 | 1996-01-29 | ||
| PCT/EP1997/000395 WO1997027863A1 (de) | 1996-01-29 | 1997-01-29 | Pharmazeutisches kombinationspräparat aus lhrh-analoga und antiöstrogenen zur behandlung von gynäcologischen störungen |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1997/000395 A-371-Of-International WO1997027863A1 (de) | 1996-01-29 | 1997-01-29 | Pharmazeutisches kombinationspräparat aus lhrh-analoga und antiöstrogenen zur behandlung von gynäcologischen störungen |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US65811300A Continuation | 1996-01-29 | 2000-09-08 | |
| US10/207,907 Continuation US20020198155A1 (en) | 1996-01-29 | 2002-07-31 | Pharmaceutical combined preparation and its use in the treatment of gynaecological disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| US20010041672A1 US20010041672A1 (en) | 2001-11-15 |
| US7309691B2 true US7309691B2 (en) | 2007-12-18 |
Family
ID=7784640
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/117,357 Expired - Fee Related US7309691B2 (en) | 1996-01-29 | 1997-01-29 | Combined pharmaceutical preparation containing LHRH-analogous substances and anti estrogens for treating gynaecological disorders |
| US09/925,419 Abandoned US20020032156A1 (en) | 1996-01-29 | 2001-08-10 | Pharmaceutical combined preparation and its use in the treatment of gynaecological disorders |
| US10/207,907 Abandoned US20020198155A1 (en) | 1996-01-29 | 2002-07-31 | Pharmaceutical combined preparation and its use in the treatment of gynaecological disorders |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/925,419 Abandoned US20020032156A1 (en) | 1996-01-29 | 2001-08-10 | Pharmaceutical combined preparation and its use in the treatment of gynaecological disorders |
| US10/207,907 Abandoned US20020198155A1 (en) | 1996-01-29 | 2002-07-31 | Pharmaceutical combined preparation and its use in the treatment of gynaecological disorders |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US7309691B2 (de) |
| EP (1) | EP0877621A1 (de) |
| JP (1) | JP2000505422A (de) |
| KR (1) | KR19990082080A (de) |
| CN (1) | CN1209750A (de) |
| BG (1) | BG63248B1 (de) |
| BR (1) | BR9707210A (de) |
| CZ (1) | CZ239198A3 (de) |
| DE (1) | DE19604231A1 (de) |
| EA (1) | EA001178B1 (de) |
| HU (1) | HUP9901288A3 (de) |
| IL (1) | IL125557A0 (de) |
| MX (1) | MX9806082A (de) |
| NO (1) | NO983465L (de) |
| PL (1) | PL328066A1 (de) |
| SK (1) | SK98798A3 (de) |
| TR (1) | TR199801452T2 (de) |
| TW (1) | TW577735B (de) |
| WO (1) | WO1997027863A1 (de) |
| ZA (1) | ZA97741B (de) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11576891B2 (en) | 2010-06-16 | 2023-02-14 | Endorecherche, Inc. | Methods of treating or preventing estrogen-related diseases |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6828415B2 (en) * | 1993-02-19 | 2004-12-07 | Zentaris Gmbh | Oligopeptide lyophilisate, their preparation and use |
| US6096764A (en) * | 1997-08-21 | 2000-08-01 | Eli Lilly And Company | Methods for inhibiting detrimental side-effects due to GnRH of GnRH agonist administration |
| CZ301912B6 (cs) | 1998-04-23 | 2010-07-28 | Zentaris Ivf Gmbh | Lécivo na lécení neplodnosti nitrodeložní inseminací |
| HUP0202429A3 (en) * | 1999-08-31 | 2004-04-28 | Schering Ag | Use of mesoprogestins (progesterone receptor modulators) for the preparation of pharmaceutical compositions for the treatment and prevention of benign hormone dependent gynecological disorders |
| US8193252B1 (en) | 1999-08-31 | 2012-06-05 | Bayer Pharma AG | Mesoprogestins (progesterone receptor modulators) for the treatment and prevention of benign hormone dependent gynecological disorders |
| US7005418B1 (en) | 1999-09-23 | 2006-02-28 | Zentaris Gmbh | Method for the therapeutic management of extrauterine proliferation of endometrial tissue, chronic pelvic pain and fallopian tube obstruction |
| PL201898B1 (pl) * | 1999-09-23 | 2009-05-29 | Zentaris Gmbh | Zastosowanie antagonisty LH-RH w leczeniu endometriozy |
| EP1297850B1 (de) * | 2000-07-05 | 2015-08-19 | Takeda Pharmaceutical Company Limited | Medizinische zusammensetzungen zur behandlung von mit sexualhormonen verbundenen erkrankungen |
| DE10050831A1 (de) | 2000-10-05 | 2002-05-02 | Veyx Pharma Gmbh | Verfahren zum Zyklusstart bei weiblichen Zuchttieren |
| IL145838A (en) * | 2000-10-16 | 2008-11-03 | Pfizer Prod Inc | Use of an estrogen agonist / antagonist to produce a drug for the treatment of vaginitis |
| WO2002056903A2 (en) * | 2001-01-17 | 2002-07-25 | Praecis Pharmaceuticals Inc. | Methods for treating hormone associated conditions using a combination of lhrh antagonists and specific estrogen receptor modulators |
| DE60239207D1 (de) * | 2001-08-10 | 2011-03-31 | Takeda Pharmaceutical | Gnrh-agonistische kombinationsmittel |
| WO2006098371A1 (ja) * | 2005-03-16 | 2006-09-21 | Masao Igarashi | 子宮内膜症および子宮腺筋症の治療剤および予防剤 |
| EP2266568A1 (de) | 2009-05-26 | 2010-12-29 | Æterna Zentaris GmbH | Pharmazeutische Zubereitung enthaltend LHRH-Antagonisten und PDE V Hemmern zur Behandlung von Sexualhormon abhängigen Erkrankungen |
| EP2266567A1 (de) | 2009-05-26 | 2010-12-29 | Æterna Zentaris GmbH | Pharmazeutische Zubereitung enthaltend Cetrorelix und PDE V Hemmern zur Behandlung von Sexualhormon abhängige Erkrankungen |
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| US5395842A (en) * | 1988-10-31 | 1995-03-07 | Endorecherche Inc. | Anti-estrogenic compounds and compositions |
| US5451590A (en) * | 1993-12-21 | 1995-09-19 | Eli Lilly & Co. | Methods of inhibiting sexual precocity |
| US5457116A (en) * | 1993-10-15 | 1995-10-10 | Eli Lilly And Company | Methods of inhibiting uterine fibrosis |
| US5593987A (en) * | 1993-12-21 | 1997-01-14 | Eli Lilly And Company | Methods of inhibiting breast disorders |
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| EP0897721A2 (de) | 1997-08-21 | 1999-02-24 | Eli Lilly And Company | Benzo(b)thiophene Derivativen zur Hemmung von durch die Verrabreichung GnRH oder GnRH-Agonisten verursachten unheilvollen Nebenwirkungen |
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1996
- 1996-01-29 DE DE19604231A patent/DE19604231A1/de not_active Ceased
-
1997
- 1997-01-29 CN CN97191940A patent/CN1209750A/zh active Pending
- 1997-01-29 SK SK987-98A patent/SK98798A3/sk unknown
- 1997-01-29 HU HU9901288A patent/HUP9901288A3/hu unknown
- 1997-01-29 JP JP9527295A patent/JP2000505422A/ja not_active Ceased
- 1997-01-29 US US09/117,357 patent/US7309691B2/en not_active Expired - Fee Related
- 1997-01-29 IL IL12555797A patent/IL125557A0/xx unknown
- 1997-01-29 WO PCT/EP1997/000395 patent/WO1997027863A1/de not_active Application Discontinuation
- 1997-01-29 EA EA199800666A patent/EA001178B1/ru not_active IP Right Cessation
- 1997-01-29 TR TR1998/01452T patent/TR199801452T2/xx unknown
- 1997-01-29 KR KR1019980705802A patent/KR19990082080A/ko not_active Application Discontinuation
- 1997-01-29 BR BR9707210A patent/BR9707210A/pt not_active IP Right Cessation
- 1997-01-29 ZA ZA9700741A patent/ZA97741B/xx unknown
- 1997-01-29 EP EP97902258A patent/EP0877621A1/de not_active Withdrawn
- 1997-01-29 PL PL97328066A patent/PL328066A1/xx unknown
- 1997-01-29 CZ CZ982391A patent/CZ239198A3/cs unknown
- 1997-02-14 TW TW086101753A patent/TW577735B/zh active
-
1998
- 1998-07-28 NO NO983465A patent/NO983465L/no not_active Application Discontinuation
- 1998-07-29 BG BG102660A patent/BG63248B1/bg unknown
- 1998-07-29 MX MX9806082A patent/MX9806082A/es unknown
-
2001
- 2001-08-10 US US09/925,419 patent/US20020032156A1/en not_active Abandoned
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2002
- 2002-07-31 US US10/207,907 patent/US20020198155A1/en not_active Abandoned
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| US5395842A (en) * | 1988-10-31 | 1995-03-07 | Endorecherche Inc. | Anti-estrogenic compounds and compositions |
| US5457116A (en) * | 1993-10-15 | 1995-10-10 | Eli Lilly And Company | Methods of inhibiting uterine fibrosis |
| US5451590A (en) * | 1993-12-21 | 1995-09-19 | Eli Lilly & Co. | Methods of inhibiting sexual precocity |
| US5552417A (en) * | 1993-12-21 | 1996-09-03 | Eli Lilly And Company | Methods of Inhibiting sexual precocity |
| US5593987A (en) * | 1993-12-21 | 1997-01-14 | Eli Lilly And Company | Methods of inhibiting breast disorders |
| US5843962A (en) * | 1993-12-21 | 1998-12-01 | Eli Lilly And Company | Methods of inhibiting ovarian dysgenesis, delayed puberty, or sexual infantilism |
| EP0897721A2 (de) | 1997-08-21 | 1999-02-24 | Eli Lilly And Company | Benzo(b)thiophene Derivativen zur Hemmung von durch die Verrabreichung GnRH oder GnRH-Agonisten verursachten unheilvollen Nebenwirkungen |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11576891B2 (en) | 2010-06-16 | 2023-02-14 | Endorecherche, Inc. | Methods of treating or preventing estrogen-related diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| HUP9901288A3 (en) | 2000-03-28 |
| US20010041672A1 (en) | 2001-11-15 |
| HUP9901288A2 (hu) | 1999-08-30 |
| NO983465L (no) | 1998-09-18 |
| PL328066A1 (en) | 1999-01-04 |
| CN1209750A (zh) | 1999-03-03 |
| US20020198155A1 (en) | 2002-12-26 |
| TR199801452T2 (xx) | 1998-10-21 |
| EP0877621A1 (de) | 1998-11-18 |
| BG63248B1 (bg) | 2001-07-31 |
| MX9806082A (es) | 1998-10-31 |
| BG102660A (en) | 1999-06-30 |
| WO1997027863A1 (de) | 1997-08-07 |
| KR19990082080A (ko) | 1999-11-15 |
| IL125557A0 (en) | 1999-03-12 |
| JP2000505422A (ja) | 2000-05-09 |
| CZ239198A3 (cs) | 1998-11-11 |
| SK98798A3 (en) | 1999-03-12 |
| NO983465D0 (no) | 1998-07-28 |
| TW577735B (en) | 2004-03-01 |
| DE19604231A1 (de) | 1997-07-31 |
| EA001178B1 (ru) | 2000-10-30 |
| ZA97741B (en) | 1997-07-30 |
| EA199800666A1 (ru) | 1999-02-25 |
| US20020032156A1 (en) | 2002-03-14 |
| BR9707210A (pt) | 1999-04-06 |
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